This study is to characterize the proteins of the human lens. The lens consists of a few very high abundance proteins become extensively modified. Methodologies have been developed to yield good separation of these proteins using two-dimensional polyacrylamide gel electrophoresis. Due to the extensive modifications, identification of the proteins is based on immunotechniques and sequencing. Normal donor lenses varying in age from fetal to 70 years and cataracts of different etiologies have been analyzed. Lens dissections yield defined populations of fiber cells from the cortex and each of the developmentally defined nuclear regions. The protein patterns in each of the cortical regions are distinguishable as cortex, with the characteristic large protein spots corresponding to each of the major crystallins. The protein patterns of the nuclear regions are all similar to each other but clearly unique from that of the cortical regions. Protein spots corresponding to the major crystallins are not readily visible. Many new spots are present, including numerous low molecular weight spots that are fragments of crystallins. The extensive crystallin modifications in the nuclear regions occur very early in the life of the lens and are not related to cataractogenesis. The protein patterns of numerous cataracts have been determined. These data are now being analyzed with respect to the cataract etiology. The proteins throughout the lens are being identified, yielding a database of information on the normal human lens.